chr12-102175518-T-A

Position:

• chr12-102175518-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017915.5(PARPBP):​c.857T>A​(p.Met286Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PARPBP NM_017915.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0380

Genes affected

PARPBP (HGNC:26074): (PARP1 binding protein) Predicted to enable DNA binding activity. Involved in negative regulation of double-strand break repair via homologous recombination. Located in chromatin and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARPBP	NM_017915.5	c.857T>A	p.Met286Lys	missense_variant	7/11	ENST00000327680.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARPBP	ENST00000327680.7	c.857T>A	p.Met286Lys	missense_variant	7/11	2	NM_017915.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2023

The c.857T>A (p.M286K) alteration is located in exon 7 (coding exon 6) of the PARPBP gene. This alteration results from a T to A substitution at nucleotide position 857, causing the methionine (M) at amino acid position 286 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.050	T;T;.
Eigen	Benign	0.095
Eigen_PC	Benign	0.070
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.62	D;D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.4	.;M;.
MutationTaster	Benign	0.99	D;D;D;D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.93	N;.;N
REVEL	Benign	0.17
Sift	Benign	0.088	T;.;T
Sift4G	Benign	0.063	T;T;T
Polyphen		0.96	D;P;.
Vest4		0.66
MutPred		0.64		Gain of catalytic residue at S359 (P = 0.0311);.;.;
MVP		0.43
ClinPred		0.89	D
GERP RS		0.54
Varity_R		0.38
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-102569296;